Computational Modeling of Realistic Cell Membranes

Abstract

Cell membranes contain a large variety of lipid types and are crowded with proteins, endowing them with the plasticity needed to fulfill their key roles in cell functioning. The compositional complexity of cellular membranes gives rise to a heterogeneous lateral organization, which is still poorly understood. Computational models, in particular molecular dynamics simulations and related techniques, have provided important insight into the organizational principles of cell membranes over the past decades. Now, we are witnessing a transition from simulations of simpler membrane models to multicomponent systems, culminating in realistic models of an increasing variety of cell types and organelles. Here, we review the state of the art in the field of realistic membrane simulations and discuss the current limitations and challenges ahead.

Protein structure prediction and design in a biologically-realistic implicit membrane

“…All-atom models are attractive because they can feature hundreds of lipid types toward approximating the composition of biological membranes (17). With current technology, detailed all-atom models can be used to explore membrane dynamics for hundreds of nanoseconds (18): the time scale required to achieve equilibrated properties on a bilayer with approximately 250 lipids (19). Coarse-grained representations such as MARTINI (20), ELBA (21), and SIRAH (22) reduce computation time by mapping atoms onto representative beads.…”

Computer simulations of protein–membrane systems

“…Following the developments in hardware and software, MD simulation have increasingly begun to capture the structural dynamics of larger macromolecular systems, like ribosomes, 57 protein-membrane systems (e.g., transporters and channels), 58,59 virus membranes, 60 and lipid rafts. 32,33 By overcoming the resolution limits of the experimental methods and exploring the fine molecular details of macromolecular events, MD simulations can now serve as molecular microscope 35,61 to investigate lipid-lipid and protein-lipid interactions of more realistic cell membranes on submillisecond timescale ( Fig. 5A).…”

Biophysical approaches for exploring lipopeptide-lipid interactions

“…In the last couple of decades, there has been a dramatic evolution in our understanding of cell membranes and the principles that govern their behavior, as experimental techniques are becoming more sophisticated. Experimental techniques and theoretical advances include improved methods for single-molecule tracking, fluorescence correlation spectroscopy, super-resolved imaging, scattering, solid-state NMR, mass spectrometry and molecular dynamics, as well as methods to prepare asymmetric model membranes and real cell membrane extracts [57,61].…”